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Stereotactic radiosurgery XVI: Isodosimetric comparison of photon stereotactic radiosurgery techniques (gamma knife vs. micromultileaf collimator linear accelerator) for acoustic neuroma--and potential clinical importance.

PURPOSE: Two stereotactic photon radiation therapy methods are currently in practice for the treatment of acoustic neuroma. In the 1990s, our data and those of others demonstrated isodosimetric advantages for gamma knife technology over linear accelerator methodology. Since then, the introduction of micromultileaf collimator technology has improved the conformity of the linear accelerator method such that the isodosimetric differences between the two techniques have narrowed. MATERIALS AND METHODS: In this study, modern gamma knife isodosimetry was compared to that of modern linac technology (conformal fixed fields and dynamic arcs) for the therapy of acoustic neuroma. This is an unusual target in that a special sensory nerve (holding the key to hearing preservation) frequently runs through the targeted volume, unlike the majority of other stereotactic radiation therapy targets. This was a single-dose prescription comparison; the perceived extra benefit of fractionation (a technique not routinely available to the gamma knife) was thereby abrogated. RESULTS: Although the gamma knife technique maintained a slight, but statistically significant, advantage with regard to dose conformity (p < 0.02) (at the debatable cost of a lower minimum target dose), the much higher internal dose gradient (high maximum dose to prescription dose [MD:PD] ratio) could be interpreted as a disadvantage with respect to hearing preservation, although advantageous with regard to tumor ablation. Of the two linac methods, the dynamic arc method gave a statistically significant advantage over the fixed-field method as regards conformity (p < 0.05), at the expense of a slightly higher brainstem dose (an average of 12.4 Gy, cf. 11.7 Gy for fixed fields), but this result was not statistically significant. No significant difference was seen in the MD:PD ratio for the two single-isocenter linac techniques. CONCLUSIONS: Gamma knife methodology remains well validated, with very good isodosimetry, but when hearing preservation is important, the improving linac technologies will compete with the gamma knife for optimal therapy. In these circumstances, the minor differences in isodosimetry between the two techniques will become important.

Humans↗

Incidence of tumours suitable for radiosurgery in a developing country like Malaysia: retrospective study done before the decision to start a radiosurgery programme.

This is a descriptive epidemiologic study that was done retrospectively for the years 1990-1996. The objective was to determine whether tumours less than 4 cm in diameter are common and thereafter suitable for radiosurgical treatment. The results showed that the incidence of brain tumours less than 4 cm in diameter was 73.3% and about 20% were situated in the eloquent area.

Adolescent↗

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases.

PURPOSE: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. METHODS: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. RESULTS: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. CONCLUSIONS: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.

Brain Neoplasms↗

Radiosurgery for brain metastases from primary lung carcinoma.

PURPOSE: Brain metastases are a common problem in patients with lung cancer. This retrospective review was performed to describe the efficacy and toxicity of stereotactic radiosurgery for brain metastases from lung carcinoma and to evaluate prognostic factors for survival. PATIENTS AND METHODS: A retrospective review was performed of 113 patients with the diagnosis of lung carcinoma who underwent radiosurgery with or without whole-brain radiotherapy for management of newly diagnosed or recurrent, single, or multiple brain metastases from 1991 through 1998 at the University of California, San Francisco. Freedom from progression and survival were measured from the date of radiosurgery and estimated using the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards models. RESULTS: The median patient age at the time of radiosurgery was 59 years (range, 37-82 years), and the median Karnofsky performance score was 90 (range, 50-100). The median survival time from radiosurgery was 12.0 months overall, 13.9 months for 41 patients treated with radiosurgery alone initially, 14.5 months for 19 patients treated with radiosurgery and whole-brain radiotherapy initially, and 10.0 months for 53 patients with recurrent brain metastases. Among newly diagnosed patients, multivariate analysis showed that improved survival was associated with absence of extracranial metastases and fewer brain metastases. Among patients with recurrent brain metastases, improved survival was associated with higher Karnofsky performance score, control of the primary tumor, and fewer metastases. Measured by lesion, 1-year local freedom from progression probabilities were 81% for radiosurgery alone, 86% for radiosurgery and whole-brain radiotherapy, and 65% for radiosurgery performed after recurrence. In patients with newly diagnosed brain metastases, there was a significantly greater risk of developing subsequent brain metastases and of worse overall brain freedom from progression after radiosurgery alone versus radiosurgery and whole-brain radiotherapy. One-year brain freedom from progression probabilities were 13% without salvage therapy and 62% with salvage therapy in the 41 patients treated initially with radiosurgery alone, versus 67% without salvage therapy and 89% with salvage therapy in the 19 patients treated initially with radiosurgery plus whole-brain radiotherapy. DISCUSSION: Radiosurgery is an effective therapy for selected patients with newly diagnosed or recurrent brain metastases from lung carcinoma. Initial whole-brain radiotherapy with radiosurgery appears to improve brain control but not survival. Prospective, randomized trials are needed to further investigate the role of radiosurgery with and without whole-brain radiotherapy for brain metastases.

Adenocarcinoma↗

Angiographic follow-up in 37 patients after radiosurgery for cerebral arteriovenous malformations as part of a multimodality treatment approach.

Modified Linac radiosurgery was utilized at our institution between 1990 and 1995 in 54 patients with cerebral arteriovenous malformations (AVMs) as part of a multimodality therapeutic approach. Most patients also underwent surgery and embolization of the AVMs prior to radiosurgery. The goal of the adjunctive radiosurgical treatment was the complete angiographic obliteration of the deep residual AVM after subtotal embolization and resection. Radiosurgery was used as the primary treatment of some small deep AVMs which were judged to have a high risk of morbidity if approached surgically. Of the 54 patients, 37 have had follow-up angiograms available for review. The median time interval between radiosurgery and the most recent angiogram was 22 months (range 5-66 months). This is a retrospective report on the angiographic follow-up available on this selected group of patients with difficult AVMs. All angiograms were evaluated for the presence of residual AVM. If any residual AVM was present, a decrease in size of more than 50% was noted as significant. The hospital and office charts of all patients were reviewed and the patients and families were contacted for up-to-date clinical follow-up. Prior to treatment, 11 patients had Spetzler-Martin grade 5 AVMs, 12 patients had grade 4 AVMs, and 14 patients had grade 3 AVMs. There were no grade 1 or 2 AVMs treated with radiosurgery. Of these 37 patients, 13 (35%) were completely obliterated on follow-up angiography. Three of the 11 (27%) grade 5 AVMs were completely obliterated. Seven of the 12 (58%) grade 4 AVMs were obliterated. Three of the 14 (21%) grade 3 AVMs have documented radiosurgical obliteration, however 8 others have had a significant decrease in size on the first posttreatment angiogram (median follow-up 14 months) and have further angiographic follow-up pending. There were 5 hemorrhages after radiosurgery, 1 was fatal and 1 resulted in permanent morbidity. Six patients have been reembolized since radiosurgery and 2 of those had their AVMs surgically resected thereafter. Only 1 patient of 6 (17%) in this series who was treated with radiosurgery alone has had documented AVM obliteration. None of 3 treated with embolization alone prior to radiosurgery have had complete obliteration. Three of the 5 patients (60%) who had only surgery prior to radiosurgery had their AVMs completely obliterated. Of the 23 patients who had all three treatments (embolization, surgery, and radiosurgery), 10 (43%) had complete obliteration of their AVMs. One patient (2%) developed moderate permanent neurological disability as a result of radiosurgery-induced necrosis. This patient did have complete obliteration of her AVM. These data support the use of radiosurgery for treatment of cerebral AVMs as part of a multimodality approach if the surgical risk of any residual AVM after embolization and microsurgical resection is deemed excessive. The adjunctive use of radiosurgery in this series resulted in the safe complete obliteration of many very difficult grade 4 and 5 AVMs. These data do not support the use of radiosurgery as the primary treatment of surgically resectable AVMs since there is a risk of interval hemorrhage and the obliteration rate is far inferior to that of microsurgical resection.

Adolescent↗

Radiosurgery of intracranial cavernous malformations.

BACKGROUND: The efficacy of radiosurgery in cases of surgically high risk symptomatic cavernous malformations (CMs) for reducing haemorrhagic risk and for seizure control has not been clearly documented and the radiation-induced complications of radiosurgery remain problematic. The authors present a retrospective clinical analysis of 22 cases of CMs treated by radiosurgery. METHODS: Twenty-two patients with symptomatic CMs were treated by linear accelerator (LINAC) radiosurgery or Gamma knife (GK) between 1995 and 1998. Medical records including radiological investigations were carefully reviewed to the last follow-up. The mean age of the patients was 34.1 years (12-56) and the male to female ratio was 12:10. Twenty patients reported at least one episode of bleeding and four had undergone microsurgery before radiosurgery. The remaining two patients presented with seizure without evidence of recent haemorrhage. In 16 cases, the CMs were deep-seated, and the others were located in the cerebral hemispheres; four were located at an eloquent area. LINAC radiosurgery using computed tomography scan was performed in 11 cases until May 1997, after which GK radiosurgery using magnetic resonance (MR) image was performed in 11 cases. The volume of the lesion ranged from 0.09 cc to 4.8 cc (mean 1.42 cc) and the mean marginal dose was 16.1 Gy (8-24). The median follow-up period after radiosurgery was 38.3 months (21-67). The rate of haemorrhage, seizure, and neurological deterioration following radiosurgery was analyzed, and the rate of haemorrhage was compared to that seen in natural course reports. FINDINGS: There was one case of haemorrhage during the follow-up period and the seizure was well controlled with anticonvulsants. In the group with prior haemorrhage, the bleeding rate of cavernous malformation after radiosurgery (1.55%/year) was lower than that of pre-radiosurgical period (35.5%/year, t=1.296, P=0.04). Six patients showed neurological deterioration following radiosurgery, however, the neurological deficits persisted in only two of the patients with LINAC. The radiosurgical modality (LINAC vs. GK) showed a possible correlation to radiation induced neurological deficits (P=0.06). On the MR images at the last follow-up, the lesion was decreased in eleven patients, increased in one, and no change was found in 10 cases. The T2 weighted MR images revealed a perilesional high signal change in nine patients. This signal change was not statistically related to lesion size (P=0.236), location (P=0.658), nor radiation dose (P=0.363), but was dependent on the treatment modality (P=0.02). New-enhancing lesion and a new cyst were each found in one case, respectively, during the follow-up. INTERPRETATION: Radiosurgery may be a good alternative option for treatment of surgically high risk CMs. However, the optimal radiosurgical technique, dose adjustment, and proper delineation of the mass are prerequisites. Radiosurgery induced complications are still problematic and post-radiosurgery MR image changes need to be further elucidated.

Adolescent↗

Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms.

OBJECTIVE: During an 8-year interval, we evaluated the survival benefit of stereotactic radiosurgery performed in 64 patients with glioblastomas multiforme (GBM) and 43 patients with anaplastic astrocytomas (AA). METHODS: Adjuvant radiosurgery was performed either before disease progression or for recurrent tumor at the time of disease progression. Clinical and imaging follow-up data were obtained for all patients. The diagnosis of GBM was obtained by performing craniotomies in 41 patients and by performing stereotactic biopsies in 23. The diagnosis of AA was obtained by performing craniotomies in 19 patients (44%) and by performing biopsies in 24. RESULTS: Of the entire series, the median survival time after initial diagnosis for patients with GBM was 26 months (standard deviation [SD], 19 mo; range, 5-79 mo) and the median survival time after radiosurgery was 16 months (SD, 16 mo; range, 1-74 mo). The 2-year survival rate was 51%. No survival benefit was identified for patients who underwent intravenously administered chemotherapy in addition to radiosurgery (P = 0.97). After undergoing radiosurgery, 12 patients (19%) underwent craniotomies and resections and 4 (6%) underwent subsequent radiosurgery for regional or remote recurrence. For 45 patients who underwent radiosurgery as part of the initial management plan, the median survival time after diagnosis was 20 months. Of the entire series, the median survival time after diagnosis for patients with anaplastic astrocytomas was 32 months (SD, 23 mo; range 5-96 mo) and the median survival time after radiosurgery was 21 months (SD, 18 mo; range 3-93 mo). The 2-year survival rate was 67%. Ten patients (23%) underwent subsequent craniotomies at a mean of 8 months after initial surgery, and two underwent subsequent radiosurgery. There was no acute neurological morbidity after radiosurgery. Histologically proven radiation necrosis occurred in one patient with GBM (1.6%) and two patients with AA (4.7%). For 21 patients for whom radiosurgery was part of the initial management plan, the median survival time after diagnosis was 56 months. CONCLUSION: In comparison to historical controls, improved survival benefit after radiosurgery was identified for patients with GBM and patients with AA. Although this survival benefit may be related to our selection of patients for radiosurgery based on their having smaller tumor volumes, no selection was made based on location. We observed that radiosurgery was safe and well tolerated. Its effectiveness as an adjuvant therapy deserves a properly stratified randomized trial.

Adolescent↗

Gamma knife radiosurgery of the brain stem cavernomas.

Over 6 years (1992-1998) 26 patients with brain stem cavernomas were treated using the Leksell gamma knife in Prague. 25 patients had a follow up of 6-66, median 24 months. Annual risk of bleeding before radiosurgery was 4%. After gamma knife treatment sudden impairment of neurodeficit reported as rebleeding was observed in 4 patients at 6-51 months, median 16.5 months, after radiosurgery. This represented a 6.8% risk of rebleeding after radiosurgery, which is not significantly different from the risk before radiosurgery. MRI or CT was performed in 24 patients 6-48, median 24, months after radiosurgery. There were no signs of rebleeding in any of the patients, nor any increase of the cavernoma. A decrease of cavernoma size was observed in 8 (33%) of patients. Temporary collateral edema after radiosurgery was detected in 5 (21%) of patients 3-12, median 11, months after radiosurgery. Neurodeficit was observed in 21 of 26 patients before radiosurgery. Improvement of the neurodeficit was detected in 9 (43%) of them 6-36, median 8, months after radiosurgery. Temporary morbidity caused by collateral edema or rebleeding occurred in 7 patients (28%) and permanent morbidity remained in 2 patients (8%). 2 patients died because of rebleeding 6 and 51 months after radiosurgery and the third patient for unrelated reason. Radiosurgery of the brain stem cavernomas was indicated when there was bleeding in the history or progressive neurodeficit and microsurgery was considered too risky. Leksell gamma knife radiosurgery of cavernomas has proved its low morbidity and zero mortality. In case of an insufficient effect of radiosurgery, or if the protective effect from rebleeding comes too late, morbidity and mortality can correspond to the natural course of the disease, as it was left without any treatment.

Adolescent↗

Judicious resection and/or radiosurgery for parasagittal meningiomas: outcomes from a multicenter review. Gamma Knife Meningioma Study Group.

BACKGROUND: Parasagittal meningiomas, especially when associated with the middle or posterior third of the superior sagittal sinus, pose difficult management challenges. Initial surgical excision is associated with high morbidity and frequent tumor recurrence after subtotal resection. Neurological deficits are cumulative when multiple resections are required. No consistent management approach exists for patients with such tumors. In addition to observation, management options include resection, stereotactic radiosurgery, or fractionated radiation therapy used alone or in combination. METHODS: Sixteen centers where resection, gamma knife radiosurgery, and/or radiation therapy were available provided management data on 203 patients with histologically benign meningiomas from the time of initial diagnosis through follow-up after radiosurgery. The timing of resections, parameters of radiosurgery, rates of tumor control, morbidity, and functional patient outcomes were studied. The median follow-up duration in this study was 3.5 years (maximum, 33 yr after presentation and 6 yr after radiosurgery). RESULTS: The tumors were located in the anterior superior sagittal sinus in 52 patients, at the middle of the sinus in 91, and at the posterior portion of the sinus in 60. The mean tumor volume at the time of radiosurgery was 10 cc. In patients who underwent radiosurgery as the primary therapy (n = 66), the 5-year actuarial tumor control rate was 93 +/- 4%. No clinical failure (need for additional therapy or worsened neurological function) occurred in patients who had smaller tumors (<7.5 cc) and who had never undergone resection (n = 41). The 5-year control rate for patients with previous surgery was only 60 +/- 10%; the control rate for the radiosurgery-treated volume was 85%. Most failures resulted from remote tumor growth. Multivariate analyses identified significantly decreased tumor control with increasing tumor volume (P = 0.002) and previous neurological deficits (P = 0.002). The rate of transient, symptomatic edema after radiosurgery was 16%, was more common with larger tumors, and occurred within 2 years. Of 33 patients who were employed at the time of radiosurgery for whom a minimum of 1 year of follow-up data were available, 30 remained employed (91%). A decrease in functional status after radiosurgery was noted in only 3 of 33 (9%) employed and 7 of 77 (9%) unemployed patients. CONCLUSION: In patients with smaller tumors (<3 cm in diameter) and patent sagittal sinuses, we advocate radiosurgery alone as the first surgical procedure. Patients with larger tumors and those with progressive neurological deficits resulting from brain compression should first undergo resection. Planned second-stage radiosurgery should be performed soon afterward for any residual tumor nodule or neoplastic dural remnant. Multimodality management may enhance long-term tumor control, reduce the need for multiple resections, and maintain the functional status of the patient.

Aged↗

Use of the Modified Rankin Scale to assess outcome after arteriovenous malformation radiosurgery.

OBJECTIVE: To present the results of arteriovenous malformation (AVM) radiosurgery using the Modified Rankin Scale (MRS) as the primary outcome measure and to analyze whether previous AVM rupture or other factors have an effect on outcomes after AVM radiosurgery. METHODS: We reviewed outcomes after AVM radiosurgery for 243 patients from 1990 and 2001. The mean follow-up after radiosurgery was 65 months. RESULTS: Forty-one patients (17%) sustained a decline in MRS (median -2) after AVM radiosurgery. We noted a decline in MRS in 4% of patients 1 year after radiosurgery, 8% of patients at 3 years after radiosurgery, and 15% of patients at 7 years after radiosurgery. The radiosurgery-based AVM score correlated with a decline in MRS after AVM radiosurgery in multivariate testing (odds ratio 2.1; 95% CI 1.2 to 3.6; p < 0.01). CONCLUSIONS: Previous AVM rupture did not influence neurologic deterioration after AVM radiosurgery. The radiosurgery-based AVM score predicted the chance of a worse MRS after radiosurgery.

Activities of Daily Living↗

The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice.

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

Animals↗